C. trachomatis proteomics: Whole genome scale mapping of C. trachomatis protective & pathogenic determinants. Chlamydia trachomatis urogenital tract infection causes inflammatory pathologies in the upper genital tract, which can lead to complications including tubal factor infertility. Understanding the pathogenic mechanisms and developing subunit vaccines have been the major focuses in modern chlamydial research. However, knowledge on chlamydial pathogenesis remains limited and there is no effective vaccine. This may be mainly due to limitations in the approaches previously used for analyzing chlamydial antigens. Although these previous approaches have provided useful information, for example, revealing the association of anti-MOMP antibody responses with protective immunity and anti-HSP60 antibody responses with pathogenesis, the results are limited in scope. To make significant advancements in understanding chlamydial pathogenic mechanisms and developing effective subunit vaccines, Dr. Zhong's lab expressed all C. trachomatis open reading frames (ORFs) as soluble fusion proteins and developed a high quality whole genome scale proteome array in the past 5 years. This array has allowed the detection of both linear and conformation-dependent human antibodies. Using this array, Dr. Zhong's lab has mapped the B cell ANTIGENome and identified novel immunodominant antigens of C. trachomatis. In the current grant, Dr. Zhong will use the whole genome scale proteome array to profile the antigen specificities of both antibody and T cell responses in C. trachomatis infected-women and to identify antigens that are associated with pathology or protective immunity. The biological relevance of the identified antigens will be characterized in both cell culture and animal model systems. Both the knowledge gained and reagents accumulated from the proposed studies will be made available to the research community. The information obtained will lay the foundation for both understanding chlamydial pathogenic mechanisms and developing diagnostic reagents and subunit vaccines. PUBLIC HEALTH RELEVANCE: By identifying and characterizing C. trachomatis antigens that are associated with pathology and protective immunity on a whole genome scale, this grant will provide the most advanced knowledge on understanding chlamydial pathogenic mechanisms, developing markers for diagnosing tubal factor infertility and constructing effective subunit vaccines.